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MicroRNA-668 alleviates renal fibrosis through PPARα/PGC-1α pathway
Xinran Wang1,2, Zhoupeng Gu3, Yan Huang4
1Department of Nephrology, The Third Xiangya Hospital, Central South University, Changsha, China.
Background:
The involvement of microRNA-668 (miR-668) in the onset and progression of renal fibrosis remains unclear. To this end, we aimed to explore the relevant mechanism of miR-668 in renal fibrosis.
Methods:
C57BL/6 J male mice were randomly divided into sham-operated, unilateral ureteral obstruction (UUO), and UUO-fenofibrate groups. Based on transfection and drug intervention, HK-2 cells were divided into blank control, TGF-β1, TGF-β1 + fenofibrate (PPARα agonist), mimics-NC, miR-668, mimics-NC + TGF-β1, miR-668 + TGF-β1, miR-668 + TGF-β1 + fenofibrate, miR-668 + TGF-β1 + GW6471 (PPARα inhibitor), mimics-NC + TGF-β1 + fenofibrate, and mimics-NC + TGF-β1 + GW6471 groups. The pathological changes in the renal tissues were observed by hematoxylin-eosin (HE) and Masson staining. The expression of PPARα, PGC-1α, miR-668, E-cadherin, Collagen III (Col III), and α-SMA in the renal tissues or HK-2 cells was detected by western blot, immunohistochemical analyses or real-time quantitative polymerase chain reaction. The regulatory effect of miR-668 on PPARα was verified by dual-luciferase reporter assay.
Results:
The expression of PPARα and PGC-1α decreased in UUO mice and TGF-β1-induced HK-2 cells, which was improved by fenofibrate. Compared to the non-transfected group, in TGF-β1-stimulated HK-2 cells, the expression of E-cadherin, PPARα and PGC-1α increased and the expression of Col III and α-SMA decreased in the miR-668-transfected group. The dual-luciferase reporter assay indicated the regulatory effect of hsa-mir-668-3p on PPARα.
Conclusion:
MiR-668 can target PPARα and positively regulate the PPARα/PGC-1α pathway to alleviate renal fibrosis.
Insights
MicroRNA-668 (miR-668) targets PPARα, activating the PPARα/PGC-1α pathway. This mechanism alleviates renal fibrosis, offering a potential therapeutic target for kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Biochemistry
Background:
- The role of microRNA-668 (miR-668) in renal fibrosis pathogenesis is not well understood.
- Investigating the molecular mechanisms underlying renal fibrosis is crucial for developing effective treatments.
Purpose of the Study:
- To elucidate the mechanism by which miR-668 influences renal fibrosis.
- To determine if miR-668 targets peroxisome proliferator-activated receptor alpha (PPARα).
Main Methods:
- Unilateral ureteral obstruction (UUO) model in C57BL/6J mice and TGF-β1-induced HK-2 cells were used.
- Expression levels of PPARα, PGC-1α, miR-668, E-cadherin, Collagen III (Col III), and α-SMA were analyzed.
- Dual-luciferase reporter assay confirmed the interaction between miR-668 and PPARα.
Main Results:
- PPARα and PGC-1α expression decreased in UUO mice and TGF-β1-treated cells, with improvement seen after fenofibrate treatment.
- miR-668 mimics increased E-cadherin, PPARα, and PGC-1α expression while decreasing Col III and α-SMA in TGF-β1-stimulated HK-2 cells.
- Dual-luciferase assay confirmed miR-668 directly targets PPARα.
Conclusions:
- MiR-668 targets PPARα and positively regulates the PPARα/PGC-1α pathway.
- MiR-668 demonstrates potential as a therapeutic agent to alleviate renal fibrosis.
